Carbamate → HCID 86667383, compound

Participants

Reaction Conditions

Reaction Steps

A solution of {1-[2-chloro-6-morpholin-4-yl-9-(tetrahydro-pyran-2-yl)-9H-purin-8-yl]-ethyl}-carbamic acid tert-butyl ester (218 mg, 0.47 mmol) in anhydrous THF (15 mL) was cooled to 0° C. Sodium hydride (60% suspension in oil, 22 mg, 0.56 mmol) was added and the mixture was stirred at 0° C. for 30 min. Iodomethane (10 vol. % solution in THF, 0.35 mL, 0.56 mmol) was added and the mixture was stirred for 16 h at RT. The reaction mixture was combined with another mixture, prepared in a similar manner from 210 mg of the carbamate starting-material, and diluted with water. After adjustment to pH7 by addition of 1M aqueous HCl and aqueous sodium bicarbonate, the mixture was extracted three times with ethyl acetate. The combined extracts were dried (Na2SO4), filtered and concentrated in vacuo, to give a 2:1 mixture of the title compound and carbamate starting-material (0.46 g). This mixture was dissolved in anhydrous THF (20 mL) and treated with sodium hydride (19 mg) and iodomethane (10 vol. % solution in THF, 0.29 mL) as before. After addition of more iodomethane (neat, 0.050 mL) and stirring for another 8 h, the reaction mixture was diluted with water, neutralized and extracted as before. The organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. The resulting residue was subjected to flash chromatography (SiO2) gradient 0-20% ethyl acetate in cyclohexane) to give {1-[2-Chloro-6-morpholin-4-yl-9-(tetrahydro-pyran-2-yl)-9H-purin-8-yl]-ethyl}-methyl-carbamic acid tert-butyl ester (316 mg, 72%). LCMS RT=4.48 min, [M+H]+=481/483

Provenance & Evidence